[Prevalence and factors associated with benzodiazepine use in children and adult inpatients]. / Prevalentie van en factoren geassocieerd met benzodiazepinegebruik tijdens opname.

BACKGROUND: Given the growing focus on deprescribing, it is crucial to thoroughly evaluate our benzodiazepine prescribing practices considering the potential risks. AIM: To investigate the prevalence and predictors of benzodiazepine prescriptions during psychiatric hospitalization and as discharge medication. METHOD: This retrospective electronic patient file study included psychiatric admissions at the UMC Utrecht between 12/01/01 and 21/04/01. Descriptive statistics were used to evaluate prevalence of benzodiazepine prescriptions in youth and adults. Multivariate regression analyses were performed to predict factors associated with benzodiazepine prescriptions and dosage. RESULTS: In total, we analyzed data from 856 admissions of youth and 4002 admissions of adults. 36.0% of the youth were prescribed benzodiazepines during admission and 14.8% at discharge. Associated factors were age (OR: 1.38) and bipolar disorder (OR: 3.98). In adults, 69.7% were prescribed benzodiazepines during admission and 37.6% at discharge. Associated factors were length of hospital stay (OR: 1.01) and anxiety disorders (OR: 2.53). Male sex, age (resp. higher and lower), and a longer length of stay predicted benzodiazepine dosages for both youth (B = 3.48; 95% CI: 0.83-0.07) and adults (B = 2.17; 95% CI: -0.04-0.05). CONCLUSION: Benzodiazepines are frequently prescribed during inpatient stays and at discharge in youth and adults, offering opportunities for deprescribing.

Retina-arrestin specific CD8+ T cells are not implicated in HLA-A29-positive birdshot chorioretinitis.

BACKGROUND: HLA-A29-positive birdshot chorioretinitis (BCR) is an inflammatory eye disorder that is generally assumed to be caused by an autoimmune response to HLA-A29-presented peptides from retinal arrestin (SAG), yet the epitopes recognized by CD8+ T cells from patients remain to be identified. OBJECTIVES: The identification of natural ligands of SAG presented by HLA-A29. To quantify CD8+ T cells reactive to antigenic SAG peptides presented by HLA-A29 in patients and controls. METHODS: We performed mass-spectrometry based immunopeptidomics of HLA-A29 of antigen-presenting cell lines from patients engineered to express SAG. MHC-I Dextramer technology was utilised to determine expansion of antigen-specific CD8+ T cells reactive to SAG peptides in complex with HLA-A29 in a cohort of BCR patients, HLA-A29-positive controls, and HLA-A29-negative controls. RESULTS: We report on the naturally presented antigenic SAG peptides identified by sequencing the HLA-A29 immunopeptidome of antigen-presenting cells of patients. We show that the N-terminally extended SAG peptide precursors can be trimmed in vitro by the antigen-processing aminopeptidases ERAP1 and ERAP2. Unexpectedly, no enhanced antigen engagement by CD8+ T cells upon stimulation with SAG peptides was observed in patients or HLA-A29-positive controls. Multiplexed HLA-A29-peptide dextramer profiling of a case-control cohort revealed that CD8+ T cells specific for these SAG peptides were neither detectable in peripheral blood nor in eye biopsies of patients. CONCLUSIONS: Collectively, these findings demonstrate that SAG is not a CD8+ T cell autoantigen and sharply contrast the paradigm in the pathogenesis of BCR. Therefore, the mechanism by which HLA-A29 is associated with BCR does not involve SAG.

Acoustic speech markers for schizophrenia-spectrum disorders: a diagnostic and symptom-recognition tool.

BACKGROUND: Clinicians routinely use impressions of speech as an element of mental status examination. In schizophrenia-spectrum disorders, descriptions of speech are used to assess the severity of psychotic symptoms. In the current study, we assessed the diagnostic value of acoustic speech parameters in schizophrenia-spectrum disorders, as well as its value in recognizing positive and negative symptoms. METHODS: Speech was obtained from 142 patients with a schizophrenia-spectrum disorder and 142 matched controls during a semi-structured interview on neutral topics. Patients were categorized as having predominantly positive or negative symptoms using the Positive and Negative Syndrome Scale (PANSS). Acoustic parameters were extracted with OpenSMILE, employing the extended Geneva Acoustic Minimalistic Parameter Set, which includes standardized analyses of pitch (F0), speech quality and pauses. Speech parameters were fed into a random forest algorithm with leave-ten-out cross-validation to assess their value for a schizophrenia-spectrum diagnosis, and PANSS subtype recognition. RESULTS: The machine-learning speech classifier attained an accuracy of 86.2% in classifying patients with a schizophrenia-spectrum disorder and controls on speech parameters alone. Patients with predominantly positive v. negative symptoms could be classified with an accuracy of 74.2%. CONCLUSIONS: Our results show that automatically extracted speech parameters can be used to accurately classify patients with a schizophrenia-spectrum disorder and healthy controls, as well as differentiate between patients with predominantly positive v. negatives symptoms. Thus, the field of speech technology has provided a standardized, powerful tool that has high potential for clinical applications in diagnosis and differentiation, given its ease of comparison and replication across samples.

[Do doctors speak a different language? The case of 'patient' without an article]. / Spreken artsen een andere taal? Het geval van 'patiënt' zonder lidwoord.

BACKGROUND: In medical speech and writing, the article before ‘patient’ is often omitted, while this would be ungrammatical in Standard Dutch. AIM: To investigate how and when the article is omitted in medical Dutch. METHOD: An online questionnaire was distributed among individuals with a medical background. RESULTS: 85 respondents participated in this study. The participants showed a strong preference to omit the definite article (‘the’) befor the word ‘patient’ and related words. This phenomenon seemed independent of the function of the word in the sentence, or of the sentence construction. However, the indefinite article (‘a’) was not omitted in the same situations. CONCLUSION: Doctors speak a different language, namely a variety of Standard Dutch in which the omission of the definite article befor ‘patient’ is preferred. We conclude that this phenomenon can be explained by recognizing ‘patient’ as a substitute for the name of the patient.

[Taal: een introductie]. / Taal: een introductie.

BACKGROUND: This special issue discusses the roles and functions of language in psychiatric practice from different perspectives. As an introduction, we discuss the phenomenon ‘language’ as an object of scientific investigation. AIM: To give a brief introduction to this theme issue. METHOD: After a terminological introduction and an outline of linguistics, we discuss some of the cognitive processes that enable humans to produce and interpret verbal utterances. RESULTS: The mental lexicon, the dictionary in our head, plays a central role in both language production and understanding. The starting point for language comprehension is recognizing basic form elements in the speech or sign stream (phonemes). Next, the perceiver must determine how words are related grammatically in order to deduce sentence meanings. We distinguish three successive steps in the production of language: conceptualizing, formulating and articulating. CONCLUSION: Production and understanding words and sentences rely on a complex interplay of cognitive processes. In communication, we use words and sentences to convey and recognize intentions. This requires close cooperation between interlocutors.

[Antipsychotic drugs for women: a narrative review and clinical guidelines]. / Antipsychotica voor vrouwen: overzicht van de literatuur en praktijkadviezen.

BACKGROUND: It has long been thought that women with a schizophrenia spectrum disorder have a more favorable course than men. However, this is not the case, even though they become ill later in life and are less likely to have comorbid drug abuse. Guidelines for prescribing antipsychotics are based on research with mostly male participants, and by following these guidelines we are doing our female patients a disservice. Gender and sex differences lead to differences in preferences, pharmacokinetics and pharmacodynamics. AIM: Providing an overview of antipsychotics for women with a schizophrenia spectrum disorder and discuss the consequences for practice. METHOD: A clinically oriented study of the literature. RESULTS: Women reach higher plasma levels than men when they receive the same dose of antipsychotic drugs (except for lurasidone and quetiapine). The effect of antipsychotics is also greater in women, because estrogens increase the brain’s dopamine sensitivity. This leads to higher risks of side effects. Clinical guidelines differ for women at different stages of life because estrogens greatly contribute to the sex differences seen in the efficacy and tolerability of antipsychotics. CONCLUSION: Clinicians should be aware that women should be treated differently with antipsychotics than men.

[Recognizing depression through computational language analysis]. / Herkennen van depressie met computationele taalanalyse.

BACKGROUND: Currently, clinical practice lacks a usable biomarker for the detection and differentiation of depression. Such a biomarker may be found in speech, from which important information can be distilled using automated speech analysis. AIM: To provide an overview of the fast-developing field of automated speech analysis for depression. METHOD: We summarize the current literature on speech features in depression. RESULTS: Current computational models can detect depression with high accuracy, rendering them applicable for diagnostic tools based on automatic speech analysis. Such tools are developing at a fast rate. CONCLUSION: Some challenges are still in the way of clinical implementation. For example, results differ largely between studies due to much variation in methodology. Furthermore, privacy and ethical issues need to be addressed before tools can be used.

[Automated speech analysis can distinguish frontotemporal dementia from depression: a pilot study]. / Geautomatiseerde spraakanalyse bij onderscheiden van frontotemporale dementie en depressie.

BACKGROUND: Differentiating the behavioural variant of frontotemporal dementia from a depression is challenging. Recent development of automated speech analyses might add to diagnostic. AIM: To investigate the value of automated speech analyses in differentiating bvFTD from a depressive disorder. METHOD: A semistructured interview was recorded in 15 patients with bvFTD, 15 patients with a depressive disorder and 15 healthy controls, which was transcribed and analysed. Acoustic and semantic values were extracted and classified using machine learning. RESULTS: Acoustic values showed an 80% accuracy for differentiating bvFTD from depressive disorder and semantic values showed an 70.8% accuracy. CONCLUSION: Acoustic as well as semantic values show significant differences between bvFTD and depressive disorder. In automated speech analyses researches should consider privacy matters as well as possible confounders like age, sex and ethnicity. This study should be repeated in a larger population.

Negative content in auditory verbal hallucinations: a natural language processing approach.

INTRODUCTION: Negative content of auditory verbal hallucinations (AVH) is a strong predictor of distress and impairment. This paper quantifies emotional voice-content in order to explore both subjective (i.e. perceived) and objectively (i.e. linguistic sentiment) measured negativity and investigates associations with distress. METHODS: Clinical and non-clinical participants with frequent AVH (n = 40) repeated and recorded their AVH verbatim directly upon hearing. The AVH were analyzed for emotional valence using Pattern, a rule-based sentiment analyzer for Dutch. The AVH of the clinical individuals were compared to those of non-clinical voice-hearers on emotional valence and associated with experienced distress. RESULTS: The mean objective valence of AVH in patients was significantly more negative than those of non-clinical voice-hearers. In the clinical individuals a larger proportion of the voice-utterances was negative (34.7% versus 18.4%) in objective valence. The linguistic valence of the AVH showed a significant, strong association with the perceived negativity, amount of distress and disruption of life, but not with the intensity of distress. CONCLUSIONS: Our results indicate that AVH of patients have a more negative linguistic content than those of non-clinical voice-hearers, which is associated with the experienced distress. Thus, patients not only perceive their voices as more negative, objective analyses confirm this.

[Improving care for women with schizophrenia-spectrum disorders]. / Vrouwen met schizofreniespectrum-stoornissen verdienen betere zorg.

Background   Women with a schizophrenia-spectrum disorder (SSD) have a better clinical profile than men at the start of their illness but lose this advantage within the first few years of living with SSD. There are benefits to be gained across different areas in the care currently offered to women with psychosis. Aim   To describe point of improvement in the care for women with SSD. Method   Review or relevant literature. Results   An important point for improvement is the early detection of female-specific signs of a first episode of psychosis, to shorten the duration of untreated psychosis, with prompt access to early intervention services. Special attention should be paid to sexual health, and to any history of childhood trauma. Antipsychotics clearly require dosing and prescription tailored to the female body, considering hormonal life phases such as menopause. Switching to prolactin-sparing medications can benefit both mental and somatic health. Finally, hormone replacement therapy should be considered for postmenopausal women. Conclusion   By providing female-specific care, women with SSD can live up to their full potential.

[Tapering of psychotropic drugs: current practice and needs of patients and their relatives]. / Deprescriptie van psychofarmaca; praktijk en behoeften van patiënten en naasten.

BACKGROUND: The prevalence of mental illness has remained stable in recent decades, yet the use of psychotropic drugs has increased. This trend suggests that psychotropic drugs are being prescribed with an unnecessary frequency. Internationally, there is growing attention for deprescribing. AIM: To investigate what experiences and needs patients and their loved ones/relatives have with regard to deprescribing of psychotropics. METHOD: An online questionnaire was distributed among members of the MIND mental health care panel, which consists of (former) patients with a psychiatric disorder and their loved ones. RESULTS: A total of 564 respondents took part in this survey. Most patients have phased out/stopped their psychotropic drugs (83.8%). This was usually done at the initiative of the patient (66.7%), in consultation with the practitioner (72.9%). The practitioner only took the initiative to deprescribe in 15.1% of the cases. In 68.6% tapering was not discussed at the start of psychotropic drug use. Patients did not experience willingness from practitioners in deprescribing, and would like to discuss deprescribing more often (79.5%). CONCLUSION: There is an undeniable demand among patients and near ones for more emphasis on deprescribing of psychotropic drugs. We advise to include this topic in the shared decision making process.

Vector-apodizing phase plate coronagraph: design, current performance, and future development [Invited].

Over the last decade, the vector-apodizing phase plate (vAPP) coronagraph has been developed from concept to on-sky application in many high-contrast imaging systems on 8 m class telescopes. The vAPP is a geometric-phase patterned coronagraph that is inherently broadband, and its manufacturing is enabled only by direct-write technology for liquid-crystal patterns. The vAPP generates two coronagraphic point spread functions (PSFs) that cancel starlight on opposite sides of the PSF and have opposite circular polarization states. The efficiency, that is, the amount of light in these PSFs, depends on the retardance offset from a half-wave of the liquid-crystal retarder. Using different liquid-crystal recipes to tune the retardance, different vAPPs operate with high efficiencies (${\gt}96\%$) in the visible and thermal infrared (0.55 µm to 5 µm). Since 2015, seven vAPPs have been installed in a total of six different instruments, including Magellan/MagAO, Magellan/MagAO-X, Subaru/SCExAO, and LBT/LMIRcam. Using two integral field spectrographs installed on the latter two instruments, these vAPPs can provide low-resolution spectra (${\rm{R}} \sim 30$) between 1 µm and 5 µm. We review the design process, development, commissioning, on-sky performance, and first scientific results of all commissioned vAPPs. We report on the lessons learned and conclude with perspectives for future developments and applications.

Ongoing transcatheter aortic valve implantation (TAVI) practice amidst a global COVID-19 crisis: nurse-led analgesia for transfemoral TAVI.

The current coronavirus disease 2019 (COVID-19) crisis has led to a relative unavailability of anaesthesiological support for non-acute cardiac care. Currently, transfemoral transcatheter aortic valve implantation (TF-TAVI) is predominantly performed as an elective catheterisation laboratory (cath lab) procedure. Hence, the performance of TAVI could come to a halt amidst the COVID-19 crisis. Our study population comprised 90 patients treated with TF-TAVI, with local analgesia performed by our dedicated cath lab nurses. The patients had a mean age of 80 ± 5 years and 59% were male, with a predicted surgical risk of 2.2 ± 0.9/3.1 ± 2.4% (Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM] score/EuroSCORE II), depicting a contemporary, lower-risk population. The composite endpoint of device success (Valve Academic Research Consortium [VARC]-2) was reached in all patients. No patients showed more than mild paravalvular leakage (3/90, 3.3%). Overall, intravenous medication was sparsely used during the procedure, with 48 of the 90 (53%) patients receiving no unplanned intravenous medication. There was neither procedural nor in-hospital mortality. The performance of TF-TAVI using local analgesia only, managed by a dedicated nurse instead of an anaesthesiologist, was shown to be feasible and safe in a selected group of patients. This strategy may (temporarily) eliminate the need for an anaesthesiologist to be present in the cath lab and enables ongoing TAVI treatment amidst the global COVID-19 crisis.

Auditory hallucinations, top-down processing and language perception: a general population study.

BACKGROUND: Studies investigating the underlying mechanisms of hallucinations in patients with schizophrenia suggest that an imbalance in top-down expectations v. bottom-up processing underlies these errors in perception. This study evaluates this hypothesis by testing if individuals drawn from the general population who have had auditory hallucinations (AH) have more misperceptions in auditory language perception than those who have never hallucinated. METHODS: We used an online survey to determine the presence of hallucinations. Participants filled out the Questionnaire for Psychotic Experiences and participated in an auditory verbal recognition task to assess both correct perceptions (hits) and misperceptions (false alarms). A hearing test was performed to screen for hearing problems. RESULTS: A total of 5115 individuals from the general Dutch population participated in this study. Participants who reported AH in the week preceding the test had a higher false alarm rate in their auditory perception compared with those without such (recent) experiences. The more recent the AH were experienced, the more mistakes participants made. While the presence of verbal AH (AVH) was predictive for false alarm rate in auditory language perception, the presence of non-verbal or visual hallucinations were not. CONCLUSIONS: The presence of AVH predicted false alarm rate in auditory language perception, whereas the presence of non-verbal auditory or visual hallucinations was not, suggesting that enhanced top-down processing does not transfer across modalities. More false alarms were observed in participants who reported more recent AVHs. This is in line with models of enhanced influence of top-down expectations in persons who hallucinate.

Factor XI deficiency enhances the pulmonary allergic response to house dust mite in mice independent of factor XII.

Asthma is associated with activation of coagulation in the airways. The coagulation system can be initiated via the extrinsic tissue factor-dependent pathway or via the intrinsic pathway, in which the central player factor XI (FXI) can be either activated via active factor XII (FXIIa) or via thrombin. We aimed to determine the role of the intrinsic coagulation system and its possible route of activation in allergic lung inflammation induced by the clinically relevant human allergen house dust mite (HDM). Wild-type (WT), FXI knockout (KO), and FXII KO mice were subjected to repeated exposure to HDM via the airways, and inflammatory responses were compared. FXI KO mice showed increased influx of eosinophils into lung tissue, accompanied by elevated local levels of the main eosinophil chemoattractant eotaxin. Although gross lung pathology and airway mucus production did not differ between groups, FXI KO mice displayed an impaired endothelial/epithelial barrier function, as reflected by elevated levels of total protein and IgM in bronchoalveolar lavage fluid. FXI KO mice had a stronger systemic IgE response with an almost completely absent HDM-specific IgG1 response. The phenotype of FXII KO mice was, except for a higher HDM-specific IgG1 response, similar to that of WT mice. In conclusion, FXI attenuates part of the allergic response to repeated administration of HDM in the airways by a mechanism that is independent of activation via FXII.

General, but not myeloid or type II lung epithelial cell, myeloid differentiation factor 88 deficiency abrogates house dust mite induced allergic lung inflammation.

Asthma is a highly prevalent chronic allergic inflammatory disease of the airways affecting people worldwide. House dust mite (HDM) is the most common allergen implicated in human allergic asthma. HDM-induced allergic responses are thought to depend upon activation of pathways involving Toll-like receptors and their adaptor protein myeloid differentiation factor 88 (MyD88). We sought here to determine the role of MyD88 in myeloid and type II lung epithelial cells in the development of asthma-like allergic disease using a mouse model. Repeated exposure to HDM caused allergic responses in control mice characterized by influx of eosinophils into the bronchoalveolar space and lung tissue, lung pathology and mucus production and protein leak into bronchoalveolar lavage fluid. All these responses were abrogated in mice with a general deficiency of MyD88 but unaltered in mice with MyD88 deficiency, specifically in myeloid or type II lung epithelial cells. We conclude that cells other than myeloid or type II lung epithelial cells are responsible for MyD88-dependent HDM-induced allergic airway inflammation.

Gate-Tunable Band Structure of the LaAlO_{3}-SrTiO_{3} Interface.

The two-dimensional electron system at the interface between LaAlO_{3} and SrTiO_{3} has several unique properties that can be tuned by an externally applied gate voltage. In this work, we show that this gate tunability extends to the effective band structure of the system. We combine a magnetotransport study on top-gated Hall bars with self-consistent Schrödinger-Poisson calculations and observe a Lifshitz transition at a density of 2.9×10^{13}cm^{-2}. Above the transition, the carrier density of one of the conducting bands decreases with increasing gate voltage. This surprising decrease is accurately reproduced in the calculations if electronic correlations are included. These results provide a clear, intuitive picture of the physics governing the electronic structure at complex-oxide interfaces.

Variation in host preferences of malaria mosquitoes is mediated by skin bacterial volatiles.

The host preferences of the anthropophilic mosquito species in the Anopheles gambiae complex (Diptera: Culicidae) are mediated by skin bacterial volatiles. However, it is not known whether these mosquitoes respond differentially to skin bacterial volatiles from non-human host species. In this study, the responses of two malaria mosquito species in the An. gambiae complex, Anopheles gambiae s.s. (hereafter, An. gambiae) and Anopheles arabiensis, with different host preferences, to volatiles released from skin bacteria were tested. Skin bacteria collected from human, cow and chicken skin significantly increased trap catches; traps containing bacteria collected from human skin caught the highest proportions of An. gambiae and An. arabiensis. Traps with bacteria of human origin caught a significantly higher proportion of An. gambiae than of An. arabiensis, whereas bacterial volatiles from the chicken attracted significantly higher numbers of An. arabiensis than of An. gambiae. Additionally, An. gambiae showed a specialized response to volatiles from four specific bacteria, whereas An. arabiensis responded equally to all species of bacteria tested. Skin bacterial volatiles may therefore play important roles in guiding mosquitoes with different host preferences. The identification of these bacterial volatiles can contribute to the development of an odour blend that attracts mosquitoes with different host preferences.